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In oral and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) exist an association between clinical and histopathological parameters with cell proliferation, basal lamina, connective tissue degradation and surrounding stroma markers. We evaluated these associations in Chilean patients. A convenience sample of 37 cases of OCSCC (n=16) and OPSCC (n=21) was analyzed clinically (TNM, clinical stage) and histologically (WHO grade of differentiation, pattern of tumor invasion). We assessed the expression of p53, Ki67, HOXA1, HOXB7, type IV collagen (ColIV) and carcinoma-associated fibroblast (α-SMA-positive cells). Additionally we conducted a univariate/bivariate analysis to assess the relationship of these variables with survival rates. Males were mostly affected (56.2% OCSCC, 76.2% OPSCC). Patients were mainly diagnosed at III/IV clinical stages (68.8% OCSCC, 90.5% OPSCC) with a predominantly infiltrative pattern invasion (62.9% OCSCC, 57.1% OPSCC). Significant association between regional lymph nodes (N) and clinical stage with OCSCC-HOXB7 expression (Chi-Square test P < 0.05) was observed. In OPSCC a statistically significant association exists between p53, Ki67 with gender (Chi-Square test P < 0.05). In OCSCC and OPSCC was statistically significant association between ki67 with HOXA1, HOXB7, and between these last two antigens (Pearson's Correlation test P < 0.05). Furthermore OPSCC-p53 showed significant correlation when it was compared with α-SMA (Kendall's Tau-c test P < 0.05). Only OCSCC-pattern invasion and OPSCC-primary tumor (T) pattern resulted associated with survival at the end of the follow up period (Chi-Square Likelihood Ratio, P < 0.05). Clinical, histological and immunohistochemical features are similar to seen in other countries. Cancer proliferation markers were associated strongly from each other. Our sample highlights prognostic value of T and pattern of invasion, but the conclusions may be limited and should be considered with caution (small sample). Many cases were diagnosed in the advanced stages of the disease, which suggests that the diagnosis of OCSCC and OPSCC is made late.

Objective: To determine the most adequate number and size of tissue microarray (TMA) cores for pleomorphic adenoma immunohistochemical studies., Study Design: Eighty-two pleomorphic adenoma cases were distributed in 3 TMA blocks assembled in triplicate containing 1.0-, 2.0-, and 3.0-mm cores. Immunohistochemical analysis against cytokeratin 7, Ki67, p63, and CD34 were performed and subsequently evaluated with PixelCount, nuclear, and microvessel software applications., Results: The 1.0-mm TMA presented lower results than 2.0- and 3.0-mm TMAs versus conventional whole section slides. Possibly because of an increased amount of stromal tissue, 3.0-mm cores presented a higher microvessel density. Comparing the results obtained with one, two, and three 2.0-mm cores, there was no difference between triplicate or duplicate TMAs and a single-core TMA., Conclusions: Considering the possible loss of cylinders during immunohistochemical reactions, 2.0-mm TMAs in duplicate are a more reliable approach for pleomorphic adenoma immunohistochemical study., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To report the clinicopathologic features of 19 oral solitary fibrous tumors (SFTs). Methods: Clinical data were collected from the records of seven pathology services. All cases were re‐evaluated by HE staining and confirmed by immunohistochemistry. Results: The series comprised 11 females (57.9%) and 8 males (42.1%), with a mean age of 47.3 ± 14.7 years (range: 22–71 years) and a 1.3:1 female‐to‐male ratio. Most tumors affected the buccal mucosa (n = 7; 36.8%) and presented clinically as an asymptomatic solitary submucosal well‐circumscribed nodule with coloration similar to the oral mucosa. Morphologically, most SFTs (n = 10; 52.6%) exhibited a classic hybrid pattern characterized by a well‐circumscribed proliferation of densely cellular areas alternating with hypocellular areas in a variably collagenous vascular stroma. Remnants of accessory salivary glands were observed in two cases (n = 2; 10.5%). All tumors were positive for STAT6 and CD34 (n = 19; 100%). Outcome information was available from 6 patients (31.6%), with clinical follow‐up ranging from 6 to 24 months (mean ± SD, 9.5 ± 6.8 months), and none developed local recurrence. Conclusions: Oral SFTs are rare and often clinically misdiagnosed. Pathologists should consider SFT in the differential diagnosis of oral spindle cell tumors. Accurate diagnosis requires careful morphological evaluation supported by immunohistochemical analysis. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor receptor 1 is a potential prognostic factor for tongue squamous cell carcinoma and is associated with oral epithelial dysplasia grade in oral leukoplakia. Methods: Thirty cases of tongue squamous cell carcinoma and 30 cases of oral leukoplakia were analyzed. Fibroblast growth factor receptor 1 and phosphorylated Akt protein expression were analyzed by immunohistochemistry and quantified using a digital algorithm. Fibroblast growth factor receptor 1 gene amplification was analyzed by fluorescent in situ hybridization in the tongue squamous cell carcinoma cases. Results: Clinical appearance and dysplasia grade were correlated with oral leukoplakia malignant transformation. Oral leukoplakia cases presenting high fibroblast growth factor receptor 1 expression showed a higher risk of malignant transformation (p = 0.016, HR: 7.3, 95% CI: 1.4–37.4). Phosphorylated Akt showed faint to no expression in oral leukoplakia, which did not correlate with dysplasia grade or malignant transformation. High expression of fibroblast growth factor receptor 1 and phosohorylated Akt were associated with poor overall survival and disease‐free survival in tongue squamous cell carcinoma, although only fibroblast growth factor receptor 1 expression was significantly associated with poor overall survival (p = 0.024; HR: 4.9, 95% CI: 1.2–19.9). Cases presenting double fibroblast growth factor receptor 1/phosphorylated Akt overexpression (n = 8) showed markedly impaired overall survival (p = 0.020; HR: 6.4, 95% CI: 1.3–31.1) and disease‐free survival (p = 0.001, HR: 13.0, 95% CI: 3.0–55.7). Fibroblast growth factor receptor 1 amplification was observed in 16.6% of tongue squamous cell carcinoma cases, being correlated with vascular and neural invasion (p = 0.001 and 0.017, respectively), but not with fibroblast growth factor receptor 1 protein expression, overall survival, or disease‐free survival. Conclusion: Fibroblast growth factor receptor 1 protein expression is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this manuscript is to present a clinicopathologic review of the literature concerning all the detailed cases of primary oral melanoma (OM) that were confirmed by immunohistochemistry. In addition, a pertinent case presentation is addressed. Data Sources: An extensive electronic search of the literature was performed using PubMed/Medline from 1953 to 2017. Relevant articles were selected based on specific inclusion criteria. Statistical analyses were conducted by the Shapiro-Wilk, Fisher's exact, chi-square, and Z tests (a = .05). Results: Forty-nine cases of primary OM reported in the literature plus the current case were analyzed; patient ages ranged from 17 to 89 years with a mean of 60.8 years; male to female ratio was 1.5:1; Caucasian patients were the most affected and the most frequent locations were maxillary alveolar mucosa and palate; the majority of the lesions were pigmented (62%); differences among the proportions of positivity to S-100, HMB-45, Melan-A, NKFC3, vimentin, tyrosinase, CK, microphthalmia transcription factor (MITF), and Ki-67 were found (P < .0001), especially when comparing with vimentin (P < .05) and CK (P < .01); recurrence was reported in 11.6% and mortality in 54.8%. The case presented is of a 71-year-old mixed-race woman who presented multiple pigmented lesions over the maxillary alveolar mucosa and palate. Positivity for S-100, HMB-45, Melan-A, and Ki-67 confirmed the diagnosis of primary OM. Conclusion: Primary OM is rare and very aggressive, with only 49 detailed cases confirmed by immunohistochemistry existing within the English literature, in addition to the present case. S-100 and HMB-45 are excellent markers to confirm the diagnosis of primary OM, although the use of adjuvant specific markers such as Melan-A, tyrosinase, and MITF should be also encouraged. [ABSTRACT FROM AUTHOR]

Background: IgG4‐related disease is a fibroinflammatory and immune‐mediated condition, which has extremely variable clinical manifestations. In this study, we aim to investigate the clinicopathological features of IgG4‐related disease involving the oral and maxillofacial region. Methods: Cases of IgG4‐related disease manifesting in the oral and maxillofacial region were retrieved from three Brazilian institutions. Clinical and serological data were obtained from the patients' medical charts, while microscopic and immunohistochemical findings were revised by oral pathologists. Diagnosis followed the American College of Rheumatology/European League against Rheumatism criteria. Results: Seven patients diagnosed with IgG4‐related disease were included in this study. Women were affected in all analysed cases, with a mean age of 55.4 years. Two patients presented with the clinical involvement of more than one oral and maxillofacial anatomic site. Therefore, our sample comprised nine oral and maxillofacial anatomic sites affected by IgG4‐related disease. The submandibular gland was affected in four cases, the tongue and the parotid gland in two cases each, and the palate in one case. In a few cases, exploratory lower lip biopsy was used as a diagnostic approach. A moderate‐to‐severe lymphoid infiltrate containing plasma cells and lymphocytes, with an increased IgG4/IgG ratio, was common. Treatment varied and steroids were the most frequently used (57.4%). Six patients remained alive, while one died from unknown causes. Conclusion: Although major salivary glands are commonly affected by IgG4‐related disease, the oral cavity can also be involved, and lower lip biopsy may be an auxiliary diagnostic tool. [ABSTRACT FROM AUTHOR]

This report describes a case of an adult rhabdomyoma (ARM) occurring in the oral cavity. A 47-year-old man was referred for the diagnosis of a painless, well-circumscribed, submucous nodule located on the floor of the mouth, measuring approximately 6.0 cm in length. Computed tomography revealed a well-defined, solid, and hypodense mass. A benign salivary gland or mesenchymal tumor were the main diagnostic hypotheses. Under local anesthesia, the patient underwent surgical excision. Microscopically, the tumor comprised large polygonal well-defined cells with abundant, eosinophilic granular cytoplasm with cross striations. No atypia or mitosis was observed. The cells were positive for muscle-specific actin, desmin, and sarcomeric alpha-actin. Based on these features, a diagnosis of ARM was established. No recurrence was observed after 48 months. Although rare, ARM should be considered in the differential diagnosis of oral submucosal nodules, especially those located on the floor of the mouth. [ABSTRACT FROM AUTHOR]

Fatty acid synthase (FASN) expression is closely related to cancer progression, in particular, tumor aggressiveness and poor prognosis. This study aimed to analyse the expression of FASN in carcinomas of the salivary glands and correlate it with Ki-67 expression. We analysed by immunohistochemistry the expression of FASN and Ki‐67 on tissue sections from 7 cases of adenocarcinoma, not otherwise specified (AdNOS), 6 cases of polymorphous adenocarcinoma (PAC), 16 cases of acinic cell carcinoma (AcCC), 19 cases of adenoid cystic carcinoma (AdCC), 15 cases of epithelial-myoepithelial carcinoma (EMC); 10 cases of secretory carcinoma (SC), 13 cases of mucoepidermoid carcinoma (MEC), 10 cases of salivary duct carcinoma (SDC) and 7 cases of myoepithelial carcinoma (MC). These carcinomas were classified into aggressive and indolent regarding their biological behaviour. Additionally, MEC and AdCC were also classified according to the histological grade. High expression of FASN was found in SDC (100%), SC (100%), AcCC (68.7%) and AdNOS (57.2%). No association was found between FASN and Ki-67 expression. Aggressive carcinomas showed a higher rate of Ki-67 proliferation (p < 0.001) and greater expression of FASN when compared to indolent carcinomas (p < 0.05). With regards to carcinomas categorized as indolent, FASN expression was much higher in the lesions that presented cell differentiation (SC and AcCC). Also, FASN expression was significantly higher in high-grade AdCC and MEC when compared to low-grade tumors (p < 0.05). We concluded that FASN expression was correlated to tumor aggressiveness and cellular differentiation in salivary gland carcinomas. [ABSTRACT FROM AUTHOR]

Background: Head and neck mucosal melanomas (MMs) are rare tumors with adverse outcomes and poorer prognoses than their more common cutaneous counterparts (cutaneous melanomas-CMs). Few studies have compared the expression of mitochondrial dynamic markers in these tumors. This study aimed to assess the correlations of mitochondrial markers with melanoma progression and their potential as predictors of lymph node involvement and distant metastasis.Methods: Immunohistochemistry against anti-mitochondrial (AMT), dynamin-related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), mitofusin-1 (MFN1), and mitofusin-2 (MFN2) antibodies was performed in 112 cases of head and neck CM and MM. A Cox regression multivariate model was used to assess the correlation of AMT, FIS1, and MFN2 expressions considering the risk for nodal and distant metastasis.Results: All markers studied presented higher staining in tumor cells than normal adjacent tissues. Higher mitochondrial content was observed in MM than in CM, and it was significantly associated with nodal metastasis in oral melanomas. Both FIS1 and DRP1 expressions were related to advanced Clark's levels in CM, and they were overexpressed in oral melanomas. Moreover, increased immunoexpression of MFN2 was significantly associated with a higher risk of metastasis in CM, and it was also overexpressed in sinonasal melanomas.Conclusions: Our results suggest that mitochondrial fission and fusion processes can play an important role during multiple stages of tumorigenesis and the development of nodal and distant metastasis in cutaneous and mucosal melanomas. [ABSTRACT FROM AUTHOR]

Background: Fatty acid synthase (FASN) is the key molecule for catalyzing fatty acid synthesis and have been associated with several malignant tumors.Methods: We analyzed the expression of FASN and Ki-67, by immunohistochemistry on 29 carcinomas ex-pleomorphic adenoma (CXPAs) and 25 pleomorphic adenomas (PAs).Results: Ki-67 proliferation index and FASN expression were significantly higher in patients with CXPA than patients with PA (P < 0.001). We found intense immunoreactivity for FASN in the malignant component of CXPAs, and these malignant areas also had intense nuclear immunoreactivity for Ki-67.Conclusions: The present results suggest that overexpression of FASN in CXPAs might be associated with malignant transformation of ductal epithelial cells and/or myoepithelial cells from PA. FASN associated with Ki-67 may be useful diagnostic markers for CXPA. [ABSTRACT FROM AUTHOR]

Mucosal melanomas are aggressive tumors, rarely observed in the oral cavity. The diagnosis is based on the clinical and microscopical features. Often these tumors had variable amounts of melanin pigmentation. However, when melanin is absent, the tumors are denominated amelanotic, presenting a tendency to misdiagnosis and delayed treatment. The aim of this study was to describe the clinicopathologic features of a series of oral amelanotic melanomas (OAM). Records of all cases of OAM were retrospectively retrieved from oral pathology services from January 2002 to January 2019. Data regarding the clinical features, morphological aspects, immunohistochemical reactions, treatment, and follow-up status were collected. Eight cases of OAM were included, 6 in men and 2 in women (ratio of 3:1) ranging in age from 33 to 77 years (mean 53.6 years). Clinically, the tumors presented as masses or ulcerated swellings. The most common intraoral locations of the tumors were gingiva and palate. Cervical lymph node metastasis was detected in 3 patients at the first examination. All but one patient died from complications of the tumors after a mean follow-up period of 8.5 months. In conclusion, OAM is a very aggressive malignant tumor, and when melanin is absent, an immunohistochemical panel comprising S100, melan A, HMB45, and SOX10 should be performed. [ABSTRACT FROM AUTHOR]

Background: Sialolipoma is a rare histological variant of lipoma commonly misdiagnosed and composed of a proliferation of mature adipocytes with secondary entrapment of normal salivary gland tissue. The purpose of the present study is to report the clinicopathologic and immunohistochemical features of 10 new cases of sialolipomas in conjunction with a review of the literature. Methods: A retrospective descriptive cross‐sectional study was performed. A total of 54,190 biopsy records of oral and maxillofacial lesions from four oral and maxillofacial pathology services in Brazil were analysed. All cases of lipomas were reviewed, and clinical, demographic and histopathological data were collected of all cases compatible with sialolipomas. In addition, immunohistochemistry stains (AE1/AE3, CK7, 34βE12, S‐100, HHF35, α‐SMA and Ki‐67) and a literature review based on a search of three electronic databases (PubMed, Web of Science and Scopus) were performed. Results: Among all lipomas reviewed, there were 10 cases of sialolipomas. The series comprised of 7 females (70.0%) and 3 males (30.0%), with a mean age of 46.1 ± 21.5 years (range: 11‐71 years) and a 2.3:1 female‐to‐male ratio. The lower lip (n = 3, 30.0%) and tongue (n = 2, 20.0%) were the most common locations, presenting clinically as a nodule of slow growth and normal colour. Conservative surgical excision was the treatment in all cases. No recurrence was observed. Conclusion: Sialolipomas are a rare histological variant of lipoma, affecting the salivary glands, mainly in the parotid gland and palate of female adults. Pathologists must recognise sialolipomas to avoid misdiagnoses with other lipomatous tumours that can affect salivary glands. [ABSTRACT FROM AUTHOR]

Objective: To analyze the gene and immunohistochemical expression of HIF‐1α, GLUT‐1, FASN, and adipophilin in normal salivary gland (NSG), pleomorphic adenoma (PA), and carcinoma ex pleomorphic adenoma (CXPA) samples. Material and Methods: The gene expression was investigated by the real‐time PCR (qRT‐PCR) method in 9 samples of frozen tissues of normal salivary gland, 13 PA, and 10 CXPA. We validated the reactions by immunohistochemistry on 20 samples from NSG, 85 PA, and 44 CXPA. Results: Our results showed that there was no statistically significant difference in HIF‐1α gene and immunohistochemistry expression among the tissues studied while FASN gene and immunohistochemistry expression increased along the carcinogenesis of the PA. GLUT‐1 was significantly more expressed in tumor tissues (PA and CXPA), although protein is mainly expressed in transformed cells than in PA and NSG. In contrast, adipophilin was significantly more expressed in NSG while the expression of the protein increased in PA and CXPA. Conclusions: In summary, the data presented here suggest that neoplastic cells reprogram the expression of GLUT‐1 and adipophilin to adapt to the tumor microenvironment and reinforce, through immunohistochemical results, a possible transcriptional and post‐translational regulatory mechanisms that act on the expression of these genes. [ABSTRACT FROM AUTHOR]

This study reports 2 odontogenic carcinosarcomas, including the clinicopathologic and immunoprofile characteristics of these rare tumors. The first case occurred in a 22-year-old male presenting a bilobular mass involving the gingiva and bone of the premolar region of the left mandible, with paresthesia of the lower lip. Microscopic examination revealed a tumor similar to ameloblastic fibrosarcoma, with atypical mesenchymal cells; however, the odontogenic epithelium also showed atypia. In the second case, a 16-year-old female had a painless, asymptomatic, large intraosseous mandibular lesion. The patient received radiotherapy to treat a rhabdomyosarcoma of the parotid 13 years before. The tumor was composed of atypical spindle cells, positive for vimentin and smooth muscle actin, intermingled with malignant odontogenic epithelium. Both epithelial and mesenchymal components of the tumors showed high index of p53- and Ki67-positive cells. The first case was diagnosed as odontogenic carcinosarcoma possibly originated from an ameloblastic fibrosarcoma, and the second as de novo odontogenic carcinosarcoma possibly caused by previous radiotherapy. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a parasitic infection transmitted by the bite of infected female sandflies. It principally affects the skin, and the frequency of mucosal involvement is about 5% to 20%. Considering the rarity of leishmaniasis affecting the upper aerodigestive tract mucosa, we evaluated the characteristics of mucocutaneous leishmaniasis and mucosal leishmaniasis and the diagnostic difficulty when the parasites are scarce in tissue samples. The clinical, histopathological, histochemical, immunohistochemical, and molecular features of 17 cases of mucocutaneous leishmaniasis and mucosal leishmaniasis were assessed. Mucosal disease was principally found in the soft palate, oropharynx, and nose, manifesting mainly as a solitary ulcer. In hematoxylin and eosin–stained sections, 10 cases revealed abundant amastigotes within the macrophages. Giemsa staining was not shown to be helpful to confirm the diagnosis in 6 cases with scarce or nondetectable amastigotes. Immunohistochemistry (IHC) showed high sensitivity by positive staining in 14 out of 17 cases (82.3%). Polymerase chain reaction was shown to be more sensitive than IHC with 13 out of 14 (92.8%) positive cases, including the 3 IHC negative cases; however, this technique is not available in many endemic regions. In summary, we suggest that the IHC is a simple technique with rapid results and relatively low cost, when compared with other laboratorial procedures; thus, IHC is a helpful tool that should be implemented in the routine diagnosis of leishmania. [ABSTRACT FROM AUTHOR]

Objective. To present 4 new cases of oral leiomyomatous hamartomas (OLH), describing its clinical, microscopical, and immunohistochemical features, and a literature review. Methods. The OLH cases were retrieved from the files of 2 Brazilian and 1 Peruvian oral pathology services. Clinical data were obtained from the pathology reports. Microscopical features were reviewed, and immunohistochemical reactions were performed. A review of the English-language literature about OLH was done. Results. The sample was composed of 3 females (4-, 10-, and 15-year-old) and 1 male (3-year-old). Three cases affected the dorsum of the tongue and one the incisive papilla, and all presented sessile or pedunculated smooth nodules. Microscopically, the lesions were composed of varying-size fascicles of smooth muscle fibers in a fibrous connective tissue background. Immunohistochemistry revealed positivity of the smooth muscle bundles for myogenic markers. The English-language literature review revealed 38 OLH cases reported, most were congenital or diagnosed up to 5 years old. The main locations were tongue and anterior maxilla. Conclusions. Although OLH is a rare lesion, it must be considered in the differential diagnosis of midline tongue or maxillary masses in newborns, infants, and youngsters. [ABSTRACT FROM AUTHOR]

Calcifying odontogenic cyst (COC) is a rare odontogenic cyst with ameloblastic epithelial lining containing clusters of ghost cells. COCs have been described in association with several odontogenic tumors, more commonly odontomas and rarely with dentigerous cyst (DC). In this article, we describe a case of COC associated with DC in a 15-year-old girl, who presented with a swelling on the right middle third of the face, producing facial asymmetry. Panoramic radiography showed a well-circumscribed, corticated, and unilocular radiolucency at the level of the right maxillary sinus, involving 2 unerupted premolars. The lesion was enucleated and histologically revealed a COC associated with DC, which presented mucous metaplasia. Immunohistochemical reactions were performed to better illustrate this rare synchronous occurrence of COC and DC, showing positivity for CK5, CK14, CK19, and p63 in both lesions. CK18 was negative in COC, and Bcl-2 was negative in DC. Periodic acid Schiff highlighted the mucous cells in the DC lining. [ABSTRACT FROM AUTHOR]

Objective: To report a case of primary diffuse large B-cell lymphoma (DLBCL) of the maxillary sinus in an 82-year-old Caucasian woman.Background: Diffuse large B-cell lymphoma of the maxillary sinus has non-specific signs and symptoms that may be confused with benign inflammatory conditions and upper respiratory infections.Methods: An incisional biopsy was performed. CD20+ /CD3- /Ki-67: 95% cells were observed.Conclusion: A good medical history, clinical and imaging evaluations and immunohistochemical reactions are crucial to establish a correct and early diagnosis of DLBCL. [ABSTRACT FROM AUTHOR]

Background: Ameloblastoma is a benign but locally aggressive odontogenic tumor, while ameloblastic carcinoma is its malignant counterpart. Angiogenesis and lymphangiogenesis in malignancies have been correlated with higher aggressiveness and poor prognosis, as well as greater expression of podoplanin by tumoral cells.Methods: Immunohistochemical expression of podoplanin, CD34, and CD105 (endoglin) was evaluated in 53 ameloblastomas and three ameloblastic carcinomas; additionally, immunohistochemistry for podoplanin was also performed in 10 tooth germs. Microvessel density of blood and lymphatic vessels was calculated and compared between ameloblastomas and ameloblastic carcinomas. Immunoexpression of podoplanin by ameloblastic cells was evaluated in tooth germs, ameloblastomas, and ameloblastic carcinomas.Results: Podoplanin was similarly expressed by odontogenic epithelial cells of tooth germs and ameloblastomas, while its expression was lower in ameloblastic carcinomas. There was no difference in microvessel density assessed by CD34 between ameloblastomas and ameloblastic carcinomas; nevertheless, the latter presented higher amounts of lymphatic and new formed blood vessels.Conclusions: Results suggest that podoplanin does not seem to be involved in invasion mechanisms of ameloblastic carcinomas, as its expression was decreased in the malignant tumoral cells. On the other hand, the increased lymphatic microvessel density and neoangiogenesis found in ameloblastic carcinomas could be related to its aggressiveness and potential for metastasis. [ABSTRACT FROM AUTHOR]

Background. Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr virus (EBV), particularly the undifferentiated nonkeratinizing subtype. Prevalence of EBV in NPC in countries such as Guatemala and Brazil has not been studied. Methods. We analyzed 19 cases of NPC, 11 from Guatemala and 8 from Brazil, for the presence of EBV by in situ hybridization and immunohistochemistry. Additionally, 19 hyperplastic adenoids from children were analyzed for EBV by in situ hybridization, 12 from Guatemala and 7 from Brazil. Results. All the NPC cases from Guatemala and 5 from Brazil were of the undifferentiated nonkeratinizing type. EBV-negative cases comprised 2 keratinizing NPC and 1 differentiated nonkeratinizing NPC. All undifferentiated nonkeratinizing NPC from both samples showed intense positivity for EBER, while LMP-1 only focally and scarcely expressed. EBER was positive in 75% and 43% of the adenoids from Guatemala and Brazil, respectively. Conclusions. All undifferentiated nonkeratinizing NPC irrespective of origin from Guatemala or Brazil were highly associated with EBV. [ABSTRACT FROM AUTHOR]

The proto-oncogene (pleomorphic adenoma gene 1 (PLAG1)) is immunohistochemically overexpressed in pleomorphic adenoma (PA). Its expression in recurrent pleomorphic adenoma (RPA), however, has not been investigated. Since complex mechanisms are involved in tumor recurrence, the aim of this study was to investigate whether PLAG1 overexpression occurs in RPA. We studied PLAG1 protein expression in 40 PAs and 36 RPAs by immunohistochemistry. Cases with immunopositive cells were classified into two categories, between 10 and 50 % and >50 %. In both groups, PLAG1 expression was observed in both epithelial and myoepithelial cells. Of PAs, 37 cases (93 %) were positive, while this was the case in 34 RPA cases (94 %). Our findings suggest that in addition to morphological similarity, PA and RPA express PLAG1, which might play a role in tumor recurrence. Furthermore, as for PA, expression of PLAG1 can be considered a valuable diagnostic marker for RPA. [ABSTRACT FROM AUTHOR]

Background: Ameloblastoma is a locally aggressive odontogenic tumor with high rates of recurrence. To better understand the molecular basis of ameloblastoma, tissue microarray (TMA) may represent a useful tool. However, despite TMA has been considered a high-throughput technique for different human neoplasms, it remains to be validated in the ameloblastoma context. Therefore, the objective of this study was to validate TMA for immunohistochemical study of ameloblastoma, determining its most appropriate design.Methods: Forty cases of ameloblastoma were manually distributed in two TMA blocks assembled in triplicate containing 1.0- and 2.0-mm cores (20 cases each). Immunohistochemistry for cytokeratins 14 and 19, and Bcl-2 and Ki-67 was performed, and semiquantitative analysis was performed. Results obtained with TMA sections were compared to their corresponding conventional whole-section slides (CWSS).Results: Kappa statistical test demonstrated that both 1.0- and 2.0-mm cores assessed as duplicate or triplicate significantly correlated with CWSS, with higher levels obtained using Ki67 (k = 0.98, 0.97, 0.88, 0.87) and CK19 (k = 0.62, 0.58, 0.85, 0.85). There was no significant difference between 1.0- and 2.0-mm cores, and between duplicate and triplicate values. 1.0-mm TMA showed a higher index of core loss (33.74% vs. 4.99%).Conclusion: Using a manual arrayer, it was demonstrated that 1.0-mm TMA arranged in duplicate is a valid method for ameloblastoma immunohistochemical study with satisfactory levels of agreement between TMA cylinders and CWSS. [ABSTRACT FROM AUTHOR]

Background: Cyclooxygenase-2 (COX-2) catalyses the conversion of arachidonic acid to prostaglandin, and its overexpression has been demonstrated in different malignant tumors, including cutaneous melanoma. However, no data about the expression of this protein in oral melanocytic lesions are available to date. The aim of this study was to evaluate the immunohistochemical expression of COX-2 in oral nevi and melanomas, comparing the results with correspondent cutaneous lesions.Methods: COX-2 was evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 36 intramucosal nevi and 13 primary oral melanomas, and in four cutaneous nevi and eight melanomas.Results: All cases of oral and cutaneous melanomas were positive for COX-2. On the other hand, all oral and cutaneous melanocytic nevi were negative.Conclusion: COX-2 is highly positive in oral melanomas and negative in oral nevi and might represent a useful marker to distinguish melanocytic lesions of the oral cavity. [ABSTRACT FROM AUTHOR]

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Background Pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor are the main entities presenting ghost cells as an important histological feature, in spite their quite different clinical presentation; it seems that they share a common pathway in the formation of these cells. The aim of this study is to examine and compare the characteristics of ghost and other cells that form these lesions. Methods Forty-three cases including 21 pilomatrixomas, 14 craniopharyngiomas, and eight calcifying cystic odontogenic tumors were evaluated by immunohistochemistry for cytokeratins, CD138, β-catenin, D2-40, Glut-1, FAS, CD10 and also by scanning electron microscopy. Results The CKs, CD138, β-catenin, Glut-1, FAS, and CD10 were more often expressed by transitional cells of craniopharyngioma and calcifying cystic odontogenic tumor, compared with pilomatrixoma. Basaloid cells of pilomatrixoma showed strong positivity for CD138 and CD10. Differences on expression pattern were identified in transitional and basal cells, as ghost cells were negative for most antibodies used, except by low expression for cytokeratins. By scanning electron microscopy, the morphology of ghost cells were similar in their fibrillar cytoplasm, but their pattern varied from sheets in pilomatrixoma to small clusters in craniopharyngioma and calcifying cystic odontogenic tumor. Conclusions Mechanisms involved in formation of ghost cells are unknown, but probably they follow different pathways as protein expression in the basal/transitional cells was not uniform in the three tumors studied. [ABSTRACT FROM AUTHOR]

Ameloblastic fibro-odontoma (AFO) is a slow-growing, expansive, benign odontogenic tumor, composed of ameloblastic epithelium embedded in an ectomesenchymal stroma resembling dental papilla, containing hard dental tissue in variable degrees of maturation, including enamel, dentin, and sometimes cementum. AFO typically affects the posterior mandible, causing bony expansion. We report a case of pigmented AFO in a 5-year-old boy, comprising clinical and histological features illustrated by immunohistochemistry using a large panel of antibodies, polarized light microscopy and scanning electron microscopy. [ABSTRACT FROM AUTHOR]

Aim To describe the clinicopathological and immuno-histochemical features of six tumours that do not fulfil the criteria of any of the currently classified odontogenic tumours. Methods and results The patients were three males and three females, whose ages ranged from 3 years to 18 years (mean, 11.05 years). In all cases there were well-defined radiolucencies associated with unerupted teeth apparently showing a pericoronal relationship. Microscopically, all tumours were composed of variably cellular loose fibrous tissue with areas similar to dental papilla, entirely surrounded by cuboidal to columnar epithelium resembling the internal epithelium of the enamel organ. Mesenchymal tissue was positive only for vimentin, and Ki67 expression was very low (<2%). The epithelium was positive for CK AE1/ AE3, CK5, CK14, and CK19, but negative for CK18 and CK20. All cases showed clear demarcation from the surrounding bone, and were surgically removed, with no recurrences after follow-up ranging from 6 months to 20 years. Conclusions These findings differ from those observed in other odontogenic lesions, such as ameloblastic fibroma, odontogenic myxoma, odontogenic fibroma, and hyperplastic dental follicles. The term primordial odontogenic tumour is proposed to describe this novel lesion. [ABSTRACT FROM AUTHOR]

Introduction Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy. Methods Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed. Results The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples. Conclusions Direct effects of radiotherapy are not able to generate morphologic changes in the microvasculature, innervation, and extracellular matrix components of the dental pulp in head and neck cancer patients. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumor (SFT) is uncommon in the oral cavity, and there are no reports in children. We report a case of a large SFT affecting the upper lip of a one year-old boy. The tumor was characterized by proliferation of spindle and multinucleated stellate-shaped cells that were intermingled between thin and thick collagen fibers. The tumor cells were diffusely positive for CD34, Bcl-2, CD99, and negative for specific muscle actin, smooth muscle actin, calponin, and caldesmon. Ki-67 labeling was less than 1%. The patient remains well after tumor excision. [ABSTRACT FROM AUTHOR]

Introduction: Basal cell carcinoma (BCC) is the most common malignant neoplasm in the skin and is considered to have a low degree of malignancy. BCC is invasive but rarely metastatic and originates in hair follicle-derived cells or interfollicular zones of the epidermis. Trichoblastoma (TB) is an infrequent benign skin neoplasm that differentiates toward follicular germinative cells. Both of these cutaneous lesions comprise nests of basaloid cells, and because the differential diagnosis is hard to obtain between them histologically due to their similarity, the correct diagnosis must be established. Materials and Methods: The sample size of this descriptive study consisted of 20 cases: 10 paraffin-embedded tissues that were diagnosed with carcinoma of solid basal cells with follicular differentiation and 10 TB tissues. The diagnosis of all samples was confirmed morphologically with hematoxylin and eosin. One-micron-thick sections were cut from each sample and analyzed semiquantitatively by immunohistochemistry (IHC). Differences in staining between BCC and TB were analyzed by Chi-square test. Results: Two of 10 TB cases were positive for Ki-67 versus 10 of 10 BCC samples. Cytokeratins 6 was expressed in 1 of 10 TB samples and in all BCC tissues. Staining with clone 34BE12 generated signals in all lesions at various intensities. Conclusion: The diagnosis between TBs and BCCs must be made histologically, because the treatment of BCC is radical and can compromise aesthetics and function, even for experienced pathologists. Because their morphological diagnosis is difficult, the histopathology results must be supported by an IHC panel. [ABSTRACT FROM AUTHOR]

Aims Mammary analogue secretory carcinoma ( MASC) of salivary glands shows morphological similarities to milk-secreting mammary epithelial cells. The aim of this study was to analyse the immunohistochemical expression of adipophilin (a component of milk lipid globule membranes) and of proteins related to secretory mechanisms ( STAT5a and mammaglobin) in MASC and other salivary tumours. Methods and results Ten cases of MASC (all with ETV6 translocation) and 83 other salivary carcinomas were studied. In all MASC cases, adipophilin stained numerous large lipid droplets. These droplets were minute in other salivary carcinomas, except for sebaceous carcinoma. Overexpression of STAT5a was detected in all MASC cases, but only occasionally in other carcinomas. Mammaglobin expression occurred frequently in MASC (70% of cases), whereas, in other carcinomas, it was uncommon and limited. Only MASC showed cytoplasmic reactivity for p63, particularly in papillary-cystic areas. Positivity for S100, vimentin and high molecular weight keratin was observed in 100% of MASC cases. Conclusions MASC is a lipid-rich tumour containing large lipid droplets covered by adipophilin. This finding can be included among its defining immunohistochemical features, and possibly represents lactation-like secretory differentiation. Strong expression of STAT5a and cytoplasmic p63 in MASC reinforces this hypothesis. [ABSTRACT FROM AUTHOR]

Abstract: Evaluation of cell cycle using antibodies against nuclear proteins involved in regulating DNA replication has gained special interest in the effort to predict biologic behavior of benign and malignant tumors. The aim of this study was to analyze the expression of minichromosome maintenance 2, Ki-67, and geminin in oral nevi and melanomas. Expression of these cell proliferation markers was evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 38 intramucosal nevi and 11 primary oral melanomas. The labeling index of each proliferation marker was assessed considering the percentage of cells expressing nuclear positivity out of the total number of cells, counting 1000 cells per slide. Minichromosome maintenance 2, Ki-67, and geminin were rarely expressed in intramucosal nevi, in contrast to oral melanomas, which showed high levels of these cell proliferation markers, particularly minichromosome maintenance 2, indicating it is a more sensitive marker in primary oral melanomas than Ki-67 and geminin. These results indicate that these markers may be involved in the pathogenesis of oral melanomas and could be eventually useful as an additional diagnostic tool for differential diagnosis of oral benign and malignant melanocytic lesions. [Copyright &y& Elsevier]

Abstract: Crystal-storing histiocytosis is a rare manifestation of plasma cell dyscrasia/monoclonal gammopathies and lymphoproliferative disorders, characterized by cytoplasmic accumulation of crystallized immunoglobulins in histiocytes. Nevertheless, some reported cases of crystal-storing histiocytosis raise the possibility that this lesion may also be reactive. Crystal-storing histiocytosis in the oral cavity is extremely rare; only one case affecting the tongue has been reported in the English-language literature. In this report, we discuss the case of a 38-year-old man who presented a persistent periapical lesion affecting the maxillary left lateral incisor. Histopathological analysis showed numerous crystal-laden histiocytes associated with a mild plasma cell infiltrate within a fibrous stroma. The plasma cells failed to show clonal light-chain restriction, and the patient had no associated hematologic disorder or systemic disease. Thus, this lesion was probably the result of hypersecretion of immunoglobulins by polyclonal plasma cells found in the periapical lesion. Crystal-storing histiocytosis should be considered in the differential diagnosis of periapical lesions. [Copyright &y& Elsevier]

Myoepithelial tumors were first described in 1943, and account for less than 1% of all salivary gland neoplasms. Their malignant variant, myoepithelial carcinoma, was first reported by Stromeyer et al. in 1975 and represents a very rare entity, characterized by distinct morphologic heterogeneity and an infiltrative growth pattern into adjacent tissues. However, there have been few reports on myoepithelial carcinoma affecting intra-oral minor salivary glands, and its immunohistochemical features have been poorly illustrated. We herein describe a rare case of myoepithelial carcinoma affecting the retromolar region of a 52-year-old woman that caused extensive mandibular bone destruction. We also reviewed the English literature concerning the involvement of intra-oral minor salivary glands by myoepithelial carcinoma. [ABSTRACT FROM AUTHOR]

Ectomesenchymal chondromyxoid tumor (ECT) is a rare benign neoplasm usually affecting the anterior dorsum of the tongue. Histopathologically, it is formed by spindle, round and/or polygonal cells embedded in a chondromyxoid matrix. Immunohistochemical positivity for vimentin, S-100 protein, glial fibrillary acid protein and neuron-specific enolase are helpful to confirm the diagnosis. There are 42 cases of ECT of the tongue reported in the English language literature, three of them showing no chondroid matrix. We describe two additional cases of ECT lacking the chondroid component, exhibiting areas of reticulated myxoid and cellular pattern. Considering the microscopical features, ECT can be classified in classic and 'chondroid-free' variants, the latter including the reticulated myxoid and cellular patterns. It is important to consider that the cellular ECT usually exhibits predominance of an infiltrative atypical cellular component that may mimic a malignant tumor. Palma Guzmán JM, de Andrade BAB, Rizo VHT, Romañach MJ, León JE, de Almeida OP. Ectomesenchymal chondromyxoid tumor: histopathologic and immunohistochemical study of two cases without a chondroid component. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Several studies have linked mast cells (MCs) with angiogenesis. The aim of this study was to correlate angiogenesis with MCs in radicular cyst (RC) and periapical granuloma (PG) cases. Methods: Forty-eight samples of periapical lesions, diagnosed as RC (n = 24) and PG (n = 24), were included. The microvessel density and microvessel area measured through the immunoexpression of CD105 and CD34 and the MC density measured through the immunoexpression of tryptase were performed. Results: MCs were detected in all RCs and PGs (P = .888), mainly in perivascular location and within fibrous stroma. CD34 stained all vessels present in all RC and PG cases. CD105 revealed differential expression, stained preferentially vessels of greater lumen, and showed variable location inside fibrous stroma in both lesions. There was a significant difference of microvessel density determinate by CD34 and CD105 in RCs (r = 0.634, P = .002) and in PGs (r = 0.5709, P = .0036). The difference was also observed when comparing age of the patient in both lesions. Considering the microscopic association between highest concentration of MCs and vascularization, CD105-positive vessels in 50% of RCs and 70.8% of PGs and CD34-positive vessels in 66.7% of RCs and 87.5% of PGs showed areas of close association with MCs. Conclusions: These results suggest differential expression of CD105 within RC and PG. There is no difference in angiogenesis and MC density between RC and PG. Moreover, because of the association between MCs with vessels and fibrous stroma, other possible roles of tryptase, in addition to the angiogenic properties, should also be considered. [Copyright &y& Elsevier]

Posttransplant lymphoproliferative disorders (PTLDs) present a wide clinicopathological spectrum, varying from the usual Epstein-Barr virus (EBV)-driven infectious mononucleosis-type polyclonal proliferations to EBV-positive or EBV-negative proliferations indistinguishable from overt lymphomas that occur in immunocompetent individuals. PTLDs characteristically have a predilection for extranodal sites and association with EBV.These disorders are usually B-cell type, although T-cell and rare cases involving both T- and B-cell types have also been described. The initial treatment consists in decreasing the immnosupressive therapy, usually with favorable results. The authors report on a rare case of a 19-year-old girl, with post—renal transplantation EBV-associated polymorphic lymphoproliferative gingival ulcerated lesions. To the best of their knowledge, this is the first case described in the English-language literature of polymorphic PTLD involving both B-cell and T-cell lineages, with an unusual immunoprofile affecting the mouth. The authors warn that this condition could be easily misdiagnosed as malignant lymphoma if not properly recognized. [ABSTRACT FROM PUBLISHER]